.alpha.-Cycloalkylalkyl substituted methanamines constitute an important class of intermediates used in the production of various substituted 2-benzoxazoles, 2-benzothiazoles, 2-oxazolpyridines and 2-thiazolopyridines, which compounds are potent leukotriene biosynthesis inhibitors. Examples of such compounds are described in commonly-owned U.S. Pat. No. 5,296,486, issued Mar. 22, 1994 and in Lazer et al, J. Med. Chem, 37, pp. 913-23 (1994). Such inhibitors are effective drugs in the treatment of particular disease states involving leukotriene biosynthesis, such as asthma.
Others have reported various synthetic schemes for the production of certain .alpha.-cycloalkylalkyl substituted methanamines and structurally similar compounds. For example, production of a racemic mixture of .alpha.-cyclohexylmethyl-2-pyridimenethanamine described in P. L. Pickard and T. L. Tolbert, J. Org. Chem., 26, pp. 4886-88 (1961). That method reacts 2-cyanopyridine with an organometallic reagent such as cyclohexylmethylmagnesium bromide to form a ketimine intermediate, which is then reduced in situ. An asymmetric synthesis of (S)-.alpha.-substituted benzylamines and pyridylamines is reported in M. Aiqiao et al., Synthetic Communications, 21, pp. 2207-12 (1991). In addition, an asymmetric synthesis of (S)-.alpha.-substituted benzylamines using ketimines derived from 2-hydroxy-3-pinanone is described in C. Yuanwei et al., Synthetic Communications, 19, pp. 1423-30 (1989). Furthermore, ketimines of 2-hydroxy-3-pinanone have been used for the synthesis of various .alpha.-amino acids and .alpha.-alkyl benzylamines (see, for example, S. I. Yamada et al., J. Chem. Soc. Chem. Comun., pp. 136-37 (1976); T. Oguri et al., Chem. Pharm. Bull., 26, pp. 803-808 (1978); A. Solladie-Cavallo and M. C. Simon, Tetrahedron Lett., 30, pp. 6011-14 (1989)).
All of these conventional methods for producing .alpha.-cycloalkylalkyl substituted methanamines and structurally related compounds suffer from one or more disadvantages, including numerous and cumbersome process steps, use of expensive or commonly unavailable reagents, low overall yields and low to moderate stereoselectivity. In addition, those conventional methods are generally not suitable for use on an industrial scale.